crossing96/oncoscreening huggingface dataset:
Survival of patients with transitional cell carcinoma of the urinary bladder in indonesia: a single institution review.	OBJECTIVE: To describe for the first time the survival of bladder transitional cell carcinoma (TCC) in Indonesia, according to clinicopathological characteristics. MATERIALS AND METHODS: Retrospective study of bladder TCC survival in a single institution, Cipto Mangunkusumo Hospital, Indonesia's national tertiary referral centre, between the years 1995 and 2005. The Kaplan-Meier method was used to determine the overall survival (OS). RESULTS: The evaluable data covered 254 cases of primary bladder TCC, in which 95 (37.4%) were non muscle-invasive bladder cancer (NMIBC), and 159 cases (62.6%) were muscle-invasive (MIBC). Of these, 105 cases (41.4%) with a follow-up period up to five years were eligible for survival analysis. The mean age was 56.5 +/- 12.1 years old, with a male to female ratio of 6:1. The 5-year OS for all bladder TCC was 27.6%, with a mean survival time of 32.6 months. For NMIBC, the 5-year OS was 53.8% with a mean survival of 54.5 months. For MIBC, the 5-year OS was 19% with a mean survival of 25.4 months. Regarding pathological stage, the 5-year OS for stage 0, I, II, III, and IV was 83.3%, 45%, 30%, 18.8%, and 9.1%, respectively. CONCLUSION: The overall survival of bladder TCC in Indonesia is low compared to other countries. Possible explanations include the high number of advanced-stage tumours at initial presentation, under-staging, significant number of treatment refusal by our patients, and the non-standardized use of adjuvant therapy in our centre.	bladder
Malignant female adnexal tumor of probable Wolffian origin: a case report.	BACKGROUND: Female adnexal tumor of probable Wolffian origin (FATWO) is a rare tumor arising in locations with Wolffian remnants, such as the broad ligament. It is thought to be a benign lesion, although this is not always the case, with scattered case reports of more aggressive behavior, sometimes years later. CASE: A rare case of disseminated malignant FATWO is presented and the literature reviewed. CONCLUSION: FATWO has the potential for malignant behavior. Familiarity with this lesion will enhance recognition. Patients need long-term follow-up.	bladder
Urothelial cancer cell response to combination therapy of gemcitabine and TRAIL.	High-risk superficial urothelial carcinoma of the bladder (UCB) is commonly treated with intravesical bacillus Calmette-Guerin (BCG), but with significant side effects. We recently showed that the tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) exhibited high therapeutic potential against UCB cells and with only limited toxic effects in normal cells. However, many cancer cells are refractory to TRAIL during monotherapy. Therefore, our experimental aim was to develop combinatorial approaches with other pro- apoptotic agents to reactivate apoptosis in resistant phenotypes. We demonstrate that UCB cells varied in their response to TRAIL, and the effect was caspase-dependent (reduced or abrogated by pre-incubation of cells with caspase-inhibitor peptides). In contrast wortmannin, a PI3K/Akt inhibitor, enhanced the TRAIL effect. Furthermore, combination therapy of TRAIL with low dose gemcitabine markedly enhanced UCB cell response (except in the TRAIL-resistant HT1376 cell line). The enhanced response was both time- and concentration-dependent and asymptotic at gemcitabine concentration >1 µmol/l. To define the mechanisms underlying gemcitabine-augmented TRAIL action, we evaluated the expression of several proteins regulating the apoptotic pathway. Gemcitabine-augmented TRAIL effect was associated with inhibition of the Bcl-2 protein (intrinsic signalling) along with activation of the caspase (extrinsic) cascade. The combined maximal stimulation of both the intrinsic and extrinsic signalling pathways also appeared to overcome the survival (PI3K/Akt) pathway as evident by the lack of response to wortmannin. Our semisolid multicellular-spheroid model showed that TRAIL and gemcitabine selectively caused UCB cells to undergo apoptosis without affecting normal cells, and both appeared to penetrate deeply enough to allow for combination intravesical therapy.	bladder
A systematic study of gene mutations in urothelial carcinoma; inactivating mutations in TSC2 and PIK3R1.	BACKGROUND: Urothelial carcinoma (UC) is characterized by frequent gene mutations of which activating mutations in FGFR3 are the most frequent. Several downstream targets of FGFR3 are also mutated in UC, e.g., PIK3CA, AKT1, and RAS. Most mutation studies of UCs have been focused on single or a few genes at the time or been performed on small sample series. This has limited the possibility to investigate co-occurrence of mutations. METHODOLOGY/PRINCIPAL FINDINGS: We performed mutation analyses of 16 genes, FGFR3, PIK3CA, PIK3R1 PTEN, AKT1, KRAS, HRAS, NRAS, BRAF, ARAF, RAF1, TSC1, TSC2, APC, CTNNB1, and TP53, in 145 cases of UC. We show that FGFR3 and PIK3CA mutations are positively associated. In addition, we identified PIK3R1 as a target for mutations. We demonstrate a negative association at borderline significance between FGFR3 and RAS mutations, and show that these mutations are not strictly mutually exclusive. We show that mutations in BRAF, ARAF, RAF1 rarely occurs in UC. Our data emphasize the possible importance of APC signaling as 6% of the investigated tumors either showed inactivating APC or activating CTNNB1 mutations. TSC1, as well as TSC2, that constitute the mTOR regulatory tuberous sclerosis complex were found to be mutated at a combined frequency of 15%. CONCLUSIONS/SIGNIFICANCE: Our data demonstrate a significant association between FGFR3 and PIK3CA mutations in UC. Moreover, the identification of mutations in PIK3R1 further emphasizes the importance of the PI3-kinase pathway in UC. The presence of TSC2 mutations, in addition to TSC1 mutations, underlines the involvement of mTOR signaling in UC.	bladder
Pazopanib synergizes with docetaxel in the treatment of bladder cancer cells.	OBJECTIVES: To investigate the efficacy of pazopanib, both alone and in combination with docetaxel, in bladder cancer cells. Bladder cancer expresses many potential therapeutic targets of biological agents, including the vascular endothelial growth factor receptor (VEGFR). Pazopanib is a small molecule inhibitor of VEGFR-1, -2-3, platelet-derived growth factor receptor (PDGFR), and c-Kit. MATERIALS AND METHODS: Using human bladder cancer cells HTB3, HT1376, J82, RT4, CRL1749, T24, Sup, and HTB9, the treatment effect of pazopanib and cytotoxic chemotherapy was assessed using a tetrazolium-based assay. The combinatorial effect of these agents on clonogenic growth was further examined. Western blotting was used to assess changes in relevant downstream targets, including phospho-AKT, phospho-FAK, total AKT, and total FAK. RESULTS: Single-agent pazopanib had modest activity. However, synergy was seen with the combination of docetaxel and pazopanib in these multiple cells lines. J82 and T24 cells were selected for additional clonogenic testing because of their resistance to single-agent docetaxel chemotherapy. 1.25 nM of docetaxel had little effect on clonogenic formation; however, in combination with pazopanib, significant inhibition of colony formation was observed. This combination treatment additionally decreased phospho-AKT, an important mediator of cell survival in all cell lines, whereas phospho-FAK expression was variably affected. CONCLUSIONS: The present study demonstrates synergistic efficacy of pazopanib with docetaxel in docetaxel-resistant bladder cancer cells. This work supports future evaluation of pazopanib with docetaxel for the treatment of bladder cancer with the potential of improved efficacy and toxicity.	bladder
Role of lymph node dissection in management of bladder cancer.	Radical cystectomy (RC) with pelvic lymph node dissection (PLND) is the gold standard for treatment of muscle-invasive bladder cancer. Recent retrospective series suggest that extended PLND provides a survival benefit, probably by removing undetected micrometastases. There have been several studies suggesting the survival benefit of extended PLND, not only for patients with node-negative disease but also for those who are node positive. The optimal boundaries of PLND seem to be at least up to the level of aortic bifurcation, including Marcille's fossa, under the present circumstances. Because retrieval of more lymph nodes may help to improve the prognosis of patients, careful approaches should be considered both surgically and pathologically. PLND should be performed for all patients who undergo RC. Prospective randomized studies will give us the answer to the question of whether extended PLND should be performed routinely.	bladder
[Recurrence of bladder cancer in remnant urethra and inguinal lymph node metastasis nine years after total cystectomy: a case report].	A 68-year-old man underwent total cystectomy, urethrectomy preserving fossa navicularis, and an Indiana pouch urinary diversion in 1997. The histopathology was UC, G3, pT4 (prostate). Nine years after the operation, he had multiple metastases to the inguinal and paraaortic lymph nodes (LNs), and he complained of erosion around the glans. Histological diagnosis of the glans revealed recurrent UC to the urethra of the glans. We considered the possibility that the inguinal LN metastasis was due to lymphatic spread from a remnant urethral recurrence. Thus, a partial penectomy and inguinal LN dissection were undertaken. Systemic chemotherapy was administered. Remnant urethral recurrence after urethrectomy preserving the fossa navicularis and inguinal LN metastasis are rare.	bladder
[Bladder preservation using chemoradiation therapy for locally invasive bladder cancer].	PURPOSE: We investigated the long-term results and molecular markers of outcome with selective organ preservation in invasive bladder cancer using chemoradiation therapy. PATIENTS AND METHODS: We examined locally invasive bladder cancer in 32 patients (30 men, 2 women; mean age at treatment 68.1 years) who underwent bladder-sparing protocols in the Department of Urology at Sumitomo Hospital between 2000 and 2005. The clinical stage was T2, T3, and T4 in 13, 16, and 3 patients, respectively. Our protocol includes aggressive transurethral resection of the bladder tumor (TURBT) and 46 Gy radiotherapy (2 Gy/fraction, 5 fractions/week) to the pelvis with concurrent cisplatin chemotherapy (20 mg/body/day, 5 days/week, the first and fourth week, intravenously). The initial evaluation included magnetic resonance imaging (MRI), urine cytology, and cystoscopy with a biopsy. During follow-up, if the patients developed superficial recurrence, they was treated with TURBT and intravesical Bacillus Calmette-Guérin (BCG), while patients with invasive recurrence were advised to undergo a salvage cystectomy. We examined the association between the expression of the Bcl-2 family in pretreatment TUR specimens and patient outcome. The mean follow-up was 54.6 months. RESULTS: The first assessment after the induction chemoradiotherapy showed that bladder preservation was achieved in 27 patients (84.4%). The actuarial local control rate with an intact bladder was 56.3% (18 patients) at 3 years. The 1-, 3-, and 5-year cancer-specific survival rate was 90.6, 84.0, and 66.9%, respectively. The 5-year cancer-specific survival rate was 75.0, 67.2, and 33.3% in T2, T3, and T4, respectively. Bcl-x positivity was significantly associated with a poor cancer-specific survival rate (log-rank test, p = 0.038). CONCLUSIONS: Chemoradiation therapy for invasive bladder cancer can achieve survival rates similar to those in patients treated with radical cystectomy, with successful bladder preservation. Our results suggest that the expression of Bcl-x is a potential prognostic marker for chemoradiation therapy in invasive bladder cancer.	bladder
[A case of asystole following povidone iodine administration].	We present a case of asystole due to anaphylactoid reaction after vaginal disinfection with povidone iodine under epidural anesthesia combined with general anesthesia. A 71-year-old woman was scheduled to undergo total cystectomy due to vesical cancer, invading into the wall of the vagina. After induction of anesthesia, epidural injection with 10 ml of 1% lidocaine and cleansing the vagina with povidone iodine solution were done at the same time. Shortly thereafter, sudden hypotension and bradycardia and asystole occurred. Multiple doses of epinephrine, chest compression, transcutaneous pacing and defibrillation were required to restore her spontaneous circulation. The surgery was cancelled. She stayed a night at the intensive care unit, and was discharged without any neurological complications the next day. The serum concentration of histamine increased to 7.0 microg x l(-1), but that of tryptase was within normal ranges when spontaneous circulation returned. The serum concentration of total iodine increased to 57.9 microg x dl(-1), which did not reach the toxic level. These results suggest that the circulatory collapse was probably caused by anaphylactoid reaction to povidone iodine. Epidural anesthesia may have worsened the circulatory collapse.	bladder
Assessing the association of pioglitazone use and bladder cancer through drug adverse event reporting.	OBJECTIVE: To analyze the association between pioglitazone use and bladder cancer through a spontaneous adverse event reporting system for medications. RESEARCH DESIGN AND METHODS: Case/noncase bladder cancer reports associated with antidiabetic drug use were retrieved from the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) between 2004 and 2009 and analyzed by the reporting odds ratio (ROR). RESULTS: Ninety-three reports of bladder cancer were retrieved, corresponding to 138 drug-reaction pairs (pioglitazone, 31; insulin, 29; metformin, 25; glimepiride, 13; exenatide, 8; others, 22). ROR was indicative of a definite risk for pioglitazone (4.30 [95% CI 2.82-6.52]), and a much weaker risk for gliclazide and acarbose, with very few cases being treated with these two drugs (6 and 4, respectively). CONCLUSIONS: In agreement with preclinical and clinical studies, AERS analysis is consistent with an association between pioglitazone and bladder cancer. This issue needs constant epidemiologic surveillance and urgent definition by more specific studies.	bladder
Lewis(y) antigen (blood group 8, BG8) is a useful marker in the histopathological differential diagnosis of flat urothelial lesions of the urinary bladder.	BACKGROUND AND AIMS: The cell-surface carbohydrate Lewis(y) antigen (blood group 8, BG8) has recently been investigated in bladder cancer, but its role in the differential diagnosis of flat urothelial lesions of the bladder has not yet been systematically evaluated. METHODS: 30 carcinoma in situ (CIS) and 30 non-CIS conditions of the bladder mucosa (four dysplasia and 26 reactive atypia according to consensus diagnoses) were comparatively assessed in terms of their Lewis(y) antigen staining profiles by two independent clinical pathologists. RESULTS: Lewis(y) antigen expression differed significantly (p<0.001) between CIS (full thickness expression throughout the entire urothelium including the basal cell layer) and non-CIS conditions (patchy discontinuous expression restricted to individual cells scattered singly throughout the urothelial mucosa). The four dysplastic study cases showed Lewis(y) antigen expression more closely related to the staining profiles observed in most of the reactive urothelial atypia. κ statistics showed excellent inter-observer agreement between both raters in terms of Lewis(y) antigen staining evaluation (κ=0.9, p<0.001). CONCLUSIONS: The data hint at the cell-surface carbohydrate Lewis(y) antigen as a so far neglected diagnostically useful marker to aid in the histological classification of conventionally equivocal flat urothelial lesions of the bladder in contemporary surgical pathology practice.	bladder
Histone deacetylases (HDACs) in XPC gene silencing and bladder cancer.	Bladder cancer is one of the most common malignancies and causes hundreds of thousands of deaths worldwide each year. Bladder cancer is strongly associated with exposure to environmental carcinogens. It is believed that DNA damage generated by environmental carcinogens and their metabolites causes development of bladder cancer. Nucleotide excision repair (NER) is the major DNA repair pathway for repairing bulk DNA damage generated by most environmental carcinogens, and XPC is a DNA damage recognition protein required for initiation of the NER process. Recent studies demonstrate reduced levels of XPC protein in tumors for a majority of bladder cancer patients. In this work we investigated the role of histone deacetylases (HDACs) in XPC gene silencing and bladder cancer development. The results of our HDAC inhibition study revealed that the treatment of HTB4 and HTB9 bladder cancer cells with the HDAC inhibitor valproic acid (VPA) caused an increase in transcription of the XPC gene in these cells. The results of our chromatin immunoprecipitation (ChIP) studies indicated that the VPA treatment caused increased binding of both CREB1 and Sp1 transcription factors at the promoter region of the XPC gene for both HTB4 and HTB9 cells. The results of our immunohistochemistry (IHC) staining studies further revealed a strong correlation between the over-expression of HDAC4 and increased bladder cancer occurrence (p < 0.001) as well as a marginal significance of increasing incidence of HDAC4 positivity seen with an increase in severity of bladder cancer (p = 0.08). In addition, the results of our caspase 3 activation studies demonstrated that prior treatment with VPA increased the anticancer drug cisplatin-induced activation of caspase 3 in both HTB4 and HTB9 cells. All of these results suggest that the HDACs negatively regulate transcription of the XPC gene in bladder cancer cells and contribute to the severity of bladder tumors.	bladder
K-Ras and β-catenin mutations cooperate with Fgfr3 mutations in mice to promote tumorigenesis in the skin and lung, but not in the bladder.	The human fibroblast growth factor receptor 3 (FGFR3) gene is frequently mutated in superficial urothelial cell carcinoma (UCC). To test the functional significance of FGFR3 activating mutations as a 'driver' of UCC, we targeted the expression of mutated Fgfr3 to the murine urothelium using Cre-loxP recombination driven by the uroplakin II promoter. The introduction of the Fgfr3 mutations resulted in no obvious effect on tumorigenesis up to 18 months of age. Furthermore, even when the Fgfr3 mutations were introduced together with K-Ras or β-catenin (Ctnnb1) activating mutations, no urothelial dysplasia or UCC was observed. Interestingly, however, owing to a sporadic ectopic Cre recombinase expression in the skin and lung of these mice, Fgfr3 mutation caused papilloma and promoted lung tumorigenesis in cooperation with K-Ras and β-catenin activation, respectively. These results indicate that activation of FGFR3 can cooperate with other mutations to drive tumorigenesis in a context-dependent manner, and support the hypothesis that activation of FGFR3 signaling contributes to human cancer.	bladder
The economics of robotic cystectomy: cost comparison of open versus robotic cystectomy.	OBJECTIVE: • To assess and compare the economic burden of open radical cystectomy (OC) vs robotic-assisted laparoscopic radical cystectomy (RC) with pelvic lymph node dissection and urinary diversion. PATIENTS AND METHODS: • A series of 103 and 83 consecutive patients undergoing OC and RC, respectively, were prospectively studied at a tertiary care institution from April 2002 to February 2009. • Data were collected on patient demographics, perioperative parameters and length of stay (LOS) in hospital. Cohorts were subdivided into ileal conduit (IC), continent cutaneous diversion (CCD) and orthotopic neobladder (ON) subgroups. • A linear cost model was created to simulate treatment with OC vs RC. Procedural costs were derived from the Medicare Resource Based Relative Value Scale. Materials costs were obtained from the respective suppliers. The indirect costs of complications were considered. • Sensitivity analyses were performed. RESULTS: • Despite a higher cost of materials, RC was less expensive than OC for IC and CCD, although the cost advantage deteriorated for ON. • The per-case costs of RC with IC, CCD and ON were $20,659, $22,102 and $22,685, respectively, compared to $25,505, $22,697 and $20,719 for their OC counterparts. • The largest cost driver in the study was LOS in hospital. • RC showed a shorter LOS compared to OC, although this effect was insufficient to offset the higher cost of robotic surgery. • Complications materially affected cost performance. CONCLUSIONS: • Despite a higher cost of materials, RC can be more cost efficient than OC as a treatment for bladder cancer at a high-volume, tertiary care referral centre, particularly with IC. • Complications significantly impact cost performance.	bladder
ERG-TMPRSS2 rearrangement is shared by concurrent prostatic adenocarcinoma and prostatic small cell carcinoma and absent in small cell carcinoma of the urinary bladder: evidence supporting monoclonal origin.	Prostatic carcinoma is a heterogeneous disease with frequent multifocality and variability in morphology. Particularly, prostatic small cell carcinoma is a rare variant with aggressive behavior. Distinction between small cell carcinoma of the prostate and urinary bladder may be challenging, especially in small biopsy specimens without associated prostatic adenocarcinoma or urothelial carcinoma. Recently, gene fusions between ETS genes, particularly ETS-related gene (ERG), and transmembrane protease, serine 2 (TMPRSS2) have been identified as a frequent event in prostate cancer. Thus, molecular methods may be helpful in determining the primary site of small cell carcinoma. Thirty cases of prostatic small cell carcinoma from the authors' archives were studied, among which 13 had concurrent prostatic adenocarcinoma. Tricolor fluorescence in situ hybridization (FISH) was performed on formalin-fixed paraffin-embedded tissue sections with a probe cocktail for 3'/5' ERG and TMPRSS2. Cases of small cell carcinoma of the bladder and conventional prostatic adenocarcinoma (25 each) were also tested as controls. ERG gene alterations were found only in prostate malignancies and not in benign prostatic tissue or bladder small cell carcinoma. TMPRSS2-ERG gene fusion was found in 47% (14/30) of prostatic small cell carcinoma. Of cases with concurrent prostatic adenocarcinoma, 85% (11/13) had identical findings in both components. In 20% of rearranged cases, the ERG abnormality was associated with 5' ERG deletion. In 17% (5/30) of cases, gain of the 21q22 locus was present. Two cases showed discordant aberrations in the small cell carcinoma and adenocarcinoma, one with deletion of 5' ERG and one with gain of chromosome 21q, both in only the adenocarcinoma component. Small cell carcinoma of the prostate demonstrates TMPRSS2-ERG rearrangement with comparable frequency to prostatic adenocarcinoma. In cases with concurrent adenocarcinoma and small cell carcinoma, the majority showed identical abnormalities in both components, indicating a likely common clonal origin. Discordant alterations were present in rare cases, suggesting that acquisition of additional genetic changes in multifocal tumors may be responsible for disease progression to a more aggressive phenotype. TMPRSS2-ERG fusion is absent in bladder small cell carcinoma, supporting the utility of FISH in distinguishing prostate from bladder primary tumors and identifying metastatic small cell carcinoma of unknown origin.	bladder